Cancers, including leukemia, are the leading cause of death in animals and humans. The exact cause of cancer is not known, but links between certain activities such as smoking or exposure to carcinogens and the incidence of certain types of cancer, such as leukemia and certain tumors has been shown by a number of researchers.
Many types of chemotherapeutic agents have been shown to be effective against cancers, tumors and leukemia, but not all types of cancer and tumor cells respond to these agents. Unfortunately, many of these agents also destroy normal cells. The exact mechanism for the action of these chemotherapeutic agents are not always known.
Despite advances in the field of cancer and leukemia treatments the leading therapies to date are radiation, chemotherapy and bone marrow transplants. Chemotherapeutic approaches are said to fight cancers that are particularly aggressive. Cytocidal or cytostatic agents work best on cancers with large growth factors, i.e., ones whose cells are rapidly dividing. To date, hormones, in particular estrogen, progesterone and testosterone, certain antibiotics produced by a variety of microbes, alkylating agents, and anti-metabolites form the bulk of therapies available to oncologists. Ideally, cytotoxic agents that have specificity for leukemia, cancer or tumor cells while not affecting normal cells would be extremely desirable. Unfortunately, none have been found and instead agents that target especially rapidly dividing cells (both diseased and normal) have been used.
Clearly, the development of materials that would target cancer or leukemia cells due to a unique specificity for them would be a breakthrough. Alternatively, materials that were cytotoxic to leukemia or cancer cells while exerting mild effects on normal cells would be desirable. Due to the above-mentioned problems in the art, the present inventor has sought improvements and provides such improvements herein.
HIV and other viral infections are also one leading cause of death. HIV is a disease in which a virus which attacks the body's immune system is replicated in the body. The HIV virus is not easily destroyed nor is there a good mechanism for keeping the host cells from replicating the virus.
Several drugs have been approved for treatment of this devastating disease, including zidovudine (AZT, Retrovir.TM.), didanosine (dideoxyinosine, ddI, Videx.TM.), stavudine (d4T, Zerit.TM.), zalcitabine (dideoxycytosine, ddC, Hivid.TM.), nevirapine (Viramune.TM.), lamivudine (Epivir.TM., 3TC), protease inhibitors, saquinavir (Invirase.TM., Fortovase.TM.), ritonavir (Norvir.TM.), nelfinavir (Viracept.TM.), efavirenz (Sustiva.TM.), abacavir (Ziagen.TM.), amprenavir (Agenerase.TM.) indinavir (Crixivan.TM.), ganciclovir, AzDU, delavirdine (Rescriptor.TM.), erythropoietin, colony stimulating factors (G-CSF and GM-CSF), non-nucleoside inhibitors, and nucleoside inhibitors. See M. I. Johnston & D. F. Hoth, Science, 260(5112), 1286-1293 (1993) and D. D. Richman, Science, 272(5270), 1886-1888 (1996 An AIDS vaccine (Salk's vaccine) has been tested and several proteins which are chemokines from CD8 have been discovered to act as HIV suppressors. In addition to the above synthetic nucleoside analogs, proteins, and antibodies, several plants and substances derived from plants have been found to have in vitro anti-HIV activity. However, HIV virus is not easily destroyed nor is there a good mechanism for keeping the host cells from replicating the virus.
Thus, medical professionals continue to search for drugs that can prevent HIV infections, treat HIV carriers to prevent them from progressing to full-blown deadly AIDS, and treat the AIDS patient. Accordingly, a material which targets the HIV virus and inhibits viral replication is highly desirable.
Herpes simplex is another viral infection which is difficult to cure. Herpes simplex virus (HSV) types 1 and 2 are persistent viruses that commonly infect humans. HSV type 1 causes oral "fever blisters" (recurrent herpes labialis), and HSV type 2 causes genital herpes, which has become a major venereal disease in many parts of the world. No fully satisfactory treatment for genital herpes currently exists. In addition, although it is uncommon, HSV can also cause encephalitis, a life-threatening infection of the brain. (The Merck Manual, Holvey, Ed., 1972; Whitley, Herpes Simplex Viruses, In: Virology, 2nd Ed., Raven Press (1990)). A most serious HSV-caused disorder is dendritic keratitis, an eye infection that produces a branched lesion of the cornea, which can in turn lead to permanent scarring and loss of vision. Ocular infections with HSV are a major cause of blindness.
Hepatitis is a disease of the human liver. It is manifested with inflammation of the liver and is usually caused by viral infections and sometimes by toxic agents. Hepatitis may progress to liver cirrhosis, liver cancer, and eventually death. Several viruses such as hepatitis A, B, C, D, E and G are known to cause various types of viral hepatitis. Among them, HBV and HCV are the most serious. HBV is a DNA virus with a virion size of 42 nm. HCV is a RNA virus with a virion size of 30-60 nm. See D. S. Chen, J. Formos. Med. Assoc., 95(1), 6-12 (1996).
Hepatitis C infects 4 to 5 times the number of people infected with HIV. Hepatitis C is difficult to treat, and it is estimated that there are 500 million people infected with it worldwide (about 15 time those infected with HIV). No effective immunization is currently available, and hepatitis C can only be controlled by other preventive measures such as improvement in hygiene and sanitary conditions and interrupting the route of transmission. At present, the only acceptable treatment for chronic hepatitis C is interferon which requires at least six (6) months of treatment and/or ribavarin which can inhibit viral replication in infected cells and also improve liver function in some people. Treatment with interferon with or without ribavarin, however, has limited long term efficacy with a response rate of about 25%.
Hepatitis B virus infection leads to a wide spectrum of liver injury. Moreover, chronic hepatitis B infection has been linked to the subsequent development of hepatocellular carcinoma, a major cause of death. Current prevention of HBV infection is a hepatitis B vaccination which is therapeutically effective. However, vaccination is not effective in treating those already infected (i.e., carriers and patients). Many drugs have been used in treating chronic hepatitis B and none have been proven to be effective, except interferon.
Treatment of HCV and HBV with interferon has limited success and has frequently been associated with adverse side effects such as fatigue, fever, chills, headache, myalgias, arthralgias, mild alopecia, psychiatric effects and associated disorders, autoimmune phenomena and associated disorders and thyroid dysfunction. Because the interferon therapy has limited efficacy and frequent adverse effects, a more effective regimen for the treatment of these viral infections is needed.
The development of materials that would target HIV infected cells or a range of viruses due to some unique specificity for them would be a breakthrough. Alternatively, materials that were cytotoxic to viruses while exerting mild side effects on normal cells would be desirable.